The evolution, impact and properties of exonic splice enhancers.
The evolution, impact and properties of exonic splice enhancers.
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DOI：
10.1186/gb-2013-14-12-r143
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发表时间：
2013-12-20
期刊：
影响因子：
12.3
通讯作者：
Hurst LD
中科院分区：
文献类型：
--
作者：
Cáceres EF;Hurst LD
在人类中，许多指定剪接位点的信息不在剪接位点。外显子剪接增强子是主要的非剪接位点基序之一。四个高通量的研究提供了一个纲要的基序，作为外显子剪接增强子的功能，但只有一个，RESCUE-ESE，已被普遍采用，以检查增强子的属性。在这里，我们考虑这四个数据集，以询问是否有任何共识的属性和外显子剪接增强子的影响。虽然只有约1%的所有六聚体基序是共同的所有分析，我们可以定义合理大小的集，发现在大多数数据集。我们认为这些共有交叉数据集反映了外显子剪接增强子的真实特性。考虑到增强子和剪接相关突变的性质的先前证据，我们询问所有数据集所考虑的外显子剪接增强子是否是嘌呤富集的;在外显子边界附近富集;能够预测相对密码子使用的趋势;在同义位点处缓慢进化;在SNP中罕见;与弱剪接位点相关;以及在较长内含子附近富集。虽然intersect数据集符合预期，但只有一个原始数据集RESCUE-ESE符合预期。出乎意料的是，一个完全实验性的数据集识别出了通常与共识相反的基序，例如，在剪接相关突变罕见的外显子核心中富集。先前使用RESCUE-ESE六聚体集的分析捕获了共有外显子剪接增强子的特性。我们估计，至少有4%的同义突变是有害的，由于增强子功能的影响。
In humans, much of the information specifying splice sites is not at the splice site. Exonic splice enhancers are one of the principle non-splice site motifs. Four high-throughput studies have provided a compendium of motifs that function as exonic splice enhancers, but only one, RESCUE-ESE, has been generally employed to examine the properties of enhancers. Here we consider these four datasets to ask whether there is any consensus on the properties and impacts of exonic splice enhancers. While only about 1% of all the identified hexamer motifs are common to all analyses we can define reasonably sized sets that are found in most datasets. These consensus intersection datasets we presume reflect the true properties of exonic splice enhancers. Given prior evidence for the properties of enhancers and splice-associated mutations, we ask for all datasets whether the exonic splice enhancers considered are purine enriched; enriched near exon boundaries; able to predict trends in relative codon usage; slow evolving at synonymous sites; rare in SNPs; associated with weak splice sites; and enriched near longer introns. While the intersect datasets match expectations, only one original dataset, RESCUE-ESE, does. Unexpectedly, a fully experimental dataset identifies motifs that commonly behave opposite to the consensus, for example, being enriched in exon cores where splice-associated mutations are rare. Prior analyses that used the RESCUE-ESE set of hexamers captured the properties of consensus exonic splice enhancers. We estimate that at least 4% of synonymous mutations are deleterious owing to an effect on enhancer functioning.
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